Western societies are struggling to pay for their ever increasing medical budgets. In the US up to 393 billion US-$ were spent in 2005 for cardiovascular diseases alone. Based on epidemiologic studies in primary prevention it is reasonable to estimate that 30% of coronary heart disease and stroke could be prevented by 2.5 hours of brisk walking per week and approximately 284,886 cardiovascular deaths could be prevented per year in the US alone. With regard to metabolic disorders the figures are even more devastating: 91% of cases of diabetes type II may be attributed to high-risk behaviour including BMI>25, low fiber/high fat diet, sedentary lifestyle, and smoking.

In today's obesogenic environment regular physical exercise is more important than ever to reduce cardiovascular events. It does so (1) by modifying classical cardiovascular risk factors and (2) by direct shear stress-mediated effects on the vascular endothelium and on the release of vascular endothelial progenitor cells (EPCs). Data from epidemiologic studies are clear: ad 1) Regular physical exercise improves glycemic control and prevents the development of overt type diabetes in patients with pathologic glucose tolerance. On a molecular basis regular exercise increases the velocity of glucose uptake into the skeletal muscle which reduces glucose levels and improves insulin action. As hyperglycemia may induce endothelial dysfunction, an improved glycemic control is directly associated with improved vasoreactivity. Regular exercise also reduces hypertension and hypercholesterolemia resulting in improved endothelial function. Ad 2) the most immediate effect of exercise on the vascular endothelium is related to the intermittent increase in blood flow, which occurs necessarily during physical activities: Endothelial cells sense even minor increases in shear stress by the deformation of their cytoskeleton and of transmembrane proteins. In recent years our understanding of the biochemical pathways activated by increased shear stress has been greatly enhanced: Today we know that the expression and the activity of the nitric oxide (NO)-producing nitric oxide synthase (NOS) is increased and that detoxification of NO-degrading oxidative radicals is enhanced.